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J Affect Disord. 2018 Feb;227:31-37. doi: 10.1016/j.jad.2017.10.027. Epub 2017 Oct 7.

Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: A nationwide population-based cohort study.

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Epidemiology and Biostatistics Consulting Center,Department of Medical Research and Department of Pharmacy, Tzu Chi General Hospital, Hualien, Taiwan.
Management Office for Health Data, China Medical University Hospital at Taichung, and College of Medicine, China Medical University, Taichung, Taiwan.
Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.
Department of Psychiatry, Tzu Chi General Hospital at Hualien, and School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address:



Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD.


Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts.


The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD.


The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD.


This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.


Bipolar disorder (BD); Systemic autoimmune diseases (SADs)

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